The present invention relates to an acetaminophen composition containing a minor amount of a pheniramine maleate, to a spray-drying method for preparing the composition and to orally administerable analgesic antihistaminic tablets formed from the composition.
Acetaminophen (hereinafter referred to sometimes as N-acetyl-p-aminophenol or simply APAP) is generally non-compressible, especially in forming orally administerable tablets. Pharmaceutical compositions containing high amounts of acetaminophen and low amounts (e.g., 2% or less) of chlorpheniramine maleate (hereinafter sometimes referred to as CPM) are available to the art. A number of such compositions (hereinafter referred to sometimes as high/low APAP/CPM compositions) are commercially available in tablet form. See Handbook of Nonprescription Drugs, Seventh Edition, 1982 (American Pharmaceutical Association, Washington, D.C.), pages 160-202, incorporated herein by reference, and Facts and Comparisons, 1983 (Facts and Comparisons Division, J. B. Lippincott Company, St. Louis, Mo.), pages 206-214b, also incorporated herein by reference.
However, tabletting of such high/low APAP/CPM compositions is troublesome from a number of standpoints. When such compositions are formed by the relatively inexpensive and simple expedient of dry-blending a large amount of APAP with a low amount of CPM, tablets formed from a given composition exhibit unacceptably high tablet-to-tablet variation in the amount of CPM therein even when the weight of the tablets is carefully controlled to provide minimal tablet-to-tablet weight variation. In attempts to reduce such tablet-to-tablet variation of the amount of CPM, such high/low APAP/CPM compositions have heretofore been prepared using wet granulation processes. However, wet granulation processes are burdensome, expensive, difficult to control and in some instances result in unacceptably high tablet-to-tablet variations in the amount of CPM in the product. Although in cmparison with dry-blending, the wet granulation methods generally result in more uniform distribution of the CPM in the bulk composition and lower tablet-to-tablet variation in the amount of CPM, substantial penalties are incurred in the form of processing which is more expensive, more time consuming and requires additional equipment and steps.
In an effort to overcome the above problems, attempts were made to prepare an acceptable spray-dried high/low APAP/CPM composition on the basis of the teaching of European patent application No. 81301709.2, published Nov. 25, 1981 under publication No. 0 040 472 A2. That application discloses spray-dried compositions comprising agglomerates of N-acetyl-p-aminophenol in a gelatinized starch matrix. As taught therein, the compositions can be prepared by spray-drying a slurry including N-acetyl-p-aminophenol and gelatinized starch and optionally including other active ingredients such as codeine salts.
Thus, an aqueous slurry was prepared containing about 90 parts APAP and about 9.5 parts pregelatinized starch (in accordance with the disclosure in that application) and further including about 0.6 part CPM dissolved therein. Thereafter, the APAP-CPM-starch slurry was spray dried and the resulting particles containing about 0.95-1.1% water were dry blended with 0.25 part stearic acid, 0.2 part sodium lauryl sulfate and 3 parts starch 1500. This procedure was repeated three times, producing three test lots of particulate blends. Tablets were prepared from each of the three blends on a tabletting press. However, tablets from each of these lots were unacceptable for one or more of the following reasons: poor friability, low maximum hardness and high disintegration time. Following these failures to achieve an entirely satisfactory solution to the previously noted problems through application of the teachings of the European patent application, the efforts based thereon were abandoned.
Accordingly, there has remained a substantial need in the art for a direct tabletting high APAP/low CPM composition which can be prepared in a simple, efficient manner and can be directly compressed into tablets having substantial tablet-to-tablet uniformity of the amount of CPM in tablets prepared with an acceptable tolerance on tablet weight, good mold release properties high hardness, low friability and low disintegration time.
It has now been found by practice of the present invention that such direct tabletting high/low APAP/CPM composition can be prepared. The composition of this invention is highly versatile, exhibiting a capability of being readily and effectively dry-blended or otherwise composited with a wide variety of other ingredients, active and inactive, and thereafter formed into tablets having substantial tablet-to-tablet uniformity of the amount of CPM, good mold release properties, and highly suitable values of hardness, disintegration, and friability.